The usual aim in developing a chemical sensor or biosensor is to produce a digital electronic signal, which is proportional to the concentration of a specific chemical or set of chemicals (analyte). The sensor usually comprises two main components, a chemical or biological part that reacts or complexes with the analyte in question (ideally specifically) to form new chemical or biological products or changes in energy that can be detected by means of the second component, a transducer. The chemical/biological component can be said to act as a receptor/indicator for the analyte. A variety of transduction methods can be used including electrochemical (such as potentiometric, amperometric, conductimetric, impedimetric), optical, calorimetric and acoustic. After transduction the signal is usually converted to an electronic digital signal.
Since the signal generated by the chemical/biological reaction with the analyte is usually dependent not only on the concentration of the analyte but also on the characteristics of the sensor itself, such sensors usually require calibration before they can be utilised quantitatively. The way in which the signal varies with the analyte concentration determines the shape of the calibration curve (signal versus analyte concentration) and may define the number of calibration points. Typical calibration curves can be straight line, exponential, s-shaped etc and the principal of calibration applies to all methodologies of transduction for chemical or biological sensors.
Calibration of sensors with an invasive medical application has its own set of specific issues. Invasive or implantable medical sensors must be presented to the patient in a sterile condition, and are often single use, disposable devices. Ideally, the sensor should be calibrated just before its use since some sensor characteristics that can affect the calibration curve vary with time (ageing effect). It is often the case that the time between sensor manufacture and use can be many months, so calibration at the point of manufacture can lead to inaccuracies in the end result. This means that the attendant clinician or nurse will be required to perform the calibration whilst maintaining sterility of the sensor. Additional constraints applied by the clinician/nurse are that the calibration process should be simple to perform, ideally invisible to the person performing the calibration, and be quickly completed (preferably in less than 10 minutes).
Calibration of many currently available medical sensors requires the clinician/nurse to carry out a number of specific steps which can lead to errors or inaccuracies in the measurement if the process is not followed correctly. There is therefore a need for a more simple calibration process, useful in connection with any invasive or implantable device, which fulfils the above discussed requirements.
Sterilisation of such devices can also provide difficulties. The sterilisation process is typically carried out at the point of manufacture to avoid difficulties with poor or incomplete sterilisation procedures at a hospital or clinic, and to save time on behalf of the clinician or nurse. Three forms of sterilisation are commonly used for the sterilisation of medical devices: steam, irradiation, and ethylene oxide. Steam is usually used for metal surgical instruments, bandages and liquids within containers but is not appropriate for devices with low melting plastic components or labile chemical or biological components since steam sterilisation usually takes place at temperatures above 116 C. Irradiation, usually gamma irradiation, is a penetrating means of sterilisation and can therefore sterilise liquids in containers but can degrade many plastics, chemicals and biological materials. This degradation is most likely to occur in the presence of water and oxygen. Ethylene oxide sterilisation is a surface sterilant that generally does not degrade the receptor and other materials that comprise a sensor, but should only be used to sterilise materials that are free from significant amounts of water, since the ethylene oxide can react with the water to form ethylene glycol. Thus ethylene oxide is the preferred means of sterilising chemical sensors.
Ethylene oxide sterilisation, however, has a number of drawbacks. Firstly, it is usual in sensor construction to immobilise the receptor to the transducer and this is usually achieved by the utilisation of polymeric materials. If the sensor is to measure water-soluble analytes, and analytes soluble in blood plasma, the polymeric immobilisation material must be hydrophilic (readily adsorb water) to allow the diffusion of the analyte through the immobilisation material to the receptor material and allow measurement to take peace. To sterilise such a sensor with ethylene oxide, all water must be removed from the hydrophilic material prior to sterilisation.
Secondly, to calibrate a sensor that is to measure a water-soluble analyte at the point of use, the user must immerse the sensor in water based solutions of the analyte (or analogues of the analyte) whilst maintaining sterile integrity. However, a calibration vessel, containing calibration solution(s), cannot be sterilised with ethylene oxide, which is a surface sterilant, and therefore must be sterilised by heat or preferably irradiation. The calibration solution(s) are therefore typically provided in separately sterilised packaging from the sensor. During calibration, sterility may be lost due to the need to break these packages to carry out the calibration process.
There is therefore also a need for a means of calibrating a sensor which avoids loss of sterility during calibration.